Crystalline form of a 4-[2-(2-fluorophenoxymethyl)phenyl]piperidine compound

Abstract

The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.

What is claimed is: 
     
       1. A method of inhibiting norepinephrine reuptake in a mammal, the method comprising administering to the mammal a norepinephrine transporter-inhibiting amount of a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)-phenyl]piperidine characterized by (a) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 17.16±0.20, and 21.78±0.20; or (b) a differential scanning calorimetry trace which has a melting point of about 196.9° C. 
     
     
       2. The method of  claim 1 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 17.16±0.20, and 21.78±0.20. 
     
     
       3. The method of  claim 2 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by having one or more additional diffraction peaks at 2θ values selected from 8.11±0.20, 13.18±0.20, 16.06±0.20, 18.38±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20. 
     
     
       4. The method of  claim 2 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in  FIG. 1 . 
     
     
       5. The method of  claim 1 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace which has a melting point of about 196.9° C. 
     
     
       6. The method of  claim 5 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace substantially in accordance with that shown in  FIG. 2 . 
     
     
       7. The method of  claim 1 , wherein the mammal is a human. 
     
     
       8. A method of inhibiting norepinephrine reuptake in a mammal, the method comprising administering to the mammal a solid pharmaceutical composition comprising a pharmaceutically acceptable carrier and a norepinephrine transporter-inhibiting amount of a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxy-methyl)phenyl]piperidine characterized by (a) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 17.16±0.20, and 21.78±0.20; or (b) a differential scanning calorimetry trace which has a melting point of about 196.9° C. 
     
     
       9. The method of  claim 8 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 17.16±0.20, and 21.78±0.20. 
     
     
       10. The method of  claim 9 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by having one or more additional diffraction peaks at 2θ values selected from 8.11±0.20, 13.18±0.20, 16.06±0.20, 18.38±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20. 
     
     
       11. The method of  claim 9 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in  FIG. 1 . 
     
     
       12. The method of  claim 8 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace which has a melting point of about 196.9° C. 
     
     
       13. The method of  claim 12 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace substantially in accordance with that shown in  FIG. 2 . 
     
     
       14. The method of  claim 8 , wherein the mammal is a human. 
     
     
       15. The method of  claim 8 , wherein the pharmaceutical composition contains about 1 milligram to about 20 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. 
     
     
       16. The method of  claim 8 , wherein the pharmaceutical composition contains about 1 milligram to about 15 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. 
     
     
       17. The method of  claim 8 , wherein the pharmaceutical composition contains about 1 milligram to about 10 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. 
     
     
       18. The method of  claim 8 , wherein the pharmaceutical composition is administered orally.